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Originally published as Genetics Published Articles Ahead of Print on January 16, 2005.
Genetics, Vol. 169, 1699-1709, March 2005, Copyright © 2005
doi:10.1534/genetics.104.033993
Combining Data From Multiple Inbred Line Crosses Improves the Power and Resolution of Quantitative Trait Loci Mapping
Renhua Li, Malcolm A. Lyons1, Henning Wittenburg2, Beverly Paigen and Gary A. Churchill3
The Jackson Laboratory, Bar Harbor, Maine 04609
3 Corresponding author: The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609.
E-mail: garyc{at}jax.org
Rodent inbred line crosses are widely used to map genetic loci associated with complex traits. This approach has proven to be powerful for detecting quantitative trait loci (QTL); however, the resolution of QTL locations, typically 
20 cM, means that hundreds of genes are implicated as potential candidates. We describe analytical methods based on linear models to combine information available in two or more inbred line crosses. Our strategy is motivated by the hypothesis that common inbred strains of the laboratory mouse are derived from a limited ancestral gene pool and thus QTL detected in multiple crosses are likely to represent shared ancestral polymorphisms. We demonstrate that the combined-cross analysis can improve the power to detect weak QTL, can narrow support intervals for QTL regions, and can be used to separate multiple QTL that colocalize by chance. Moreover, combined-cross analysis can establish the allelic states of a QTL among a set of parental lines, thus providing critical information for narrowing QTL regions by haplotype analysis.
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